A Biomechanical Study of Patterning During Gut Development

In order to efficiently pack the lengthy small intestine into the body cavity, the developing vertebrate gut tube forms a reproducible looped pattern as it grows. We previously determined that gut looping morphogenesis is driven by the forces that arise from the differential growth between the gut tube and the anchoring dorsal mesenteric sheet. While the looping pattern provides an artful mechanism for fitting a longer tube into the body, undoubtedly contributing to the luminal surface area necessary for optimal nutrient absorption, one can imagine alternative mechanisms of increasing surface area such as modifying the morphology of the luminal tissue. The lumen of the intestine is covered with finger‐like projections termed villi which serve to dramatically increase the surface area of the intestine. Although very little is known about the mechanism driving villi morphogenesis, the formation of villi has previously been explored at a descriptive level in chick. During this process in chick, the intestine undergoes multiple phases of morphogenesis, beginning with the formation of longitudinally oriented ridges, which appear as an inward buckling of the luminal surface of the tube. These ridges become kinked with regular and uniform periodicity appearing as raised zigzags. These zigzags then enlarge and flatten at which point definitive villi become visible in a specific, predetermined pattern along the zigzags. We hypothesize that tissue‐level forces from the smooth muscle layers lead to these striking patterns seen in the compressed mesenchyme and attached endoderm. These same forces appear to instigate patterns of signaling necessary for outgrowth of definitive villi from the zigzag pattern. Additionally, these signaling environments delineated by tissue‐level forces may be essential for directing the location of adult intestinal stem cell markers during the morphogenesis of villi and crypts.